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The approval is supported by data from the pivotal phase 3 ARANOTE trial.
The FDA has approved darolutamide (Nubeqa) for the treatment of adult patients with metastatic castration-sensitive prostate cancer (mCSPC), the agency announced in a news release.1
Darolutamide plus ADT led to an improvement in rPFS vs placebo plus ADT in patients with mCSPC.
With this approval, darolutamide becomes the first androgen receptor inhibitor approved for use in patients with mCSPC with or without chemotherapy.
Darolutamide is also indicated in the US for use in combination with and without docetaxel in adult patients with mCSPC, as well as for the treatment of adult patients with non-metastatic castration-resistant prostate cancer.
"Clinical data from the ARANOTE trial supporting this new regimen showed that NUBEQA plus ADT demonstrated powerful efficacy in men with mCSPC. Today’s approval further expands physicians’ options for using NUBEQA with and without docetaxel in this setting, providing a potential new choice for patients," said Fred Saad, MD, professor and chairman of surgery and director of genitourinary oncology at the University of Montreal Hospital Center and principal investigator of the ARANOTE trial, in a news release from Bayer.2
According to the FDA, the recommended dose for darolutamide is 600 mg taken orally, twice daily, with food until disease progression or unacceptable toxicity.
The approval is supported by data from the pivotal phase 3 ARANOTE trial (NCT04736199), which showed that darolutamide plus ADT significantly extended radiographic progression-free survival (rPFS) compared with placebo plus ADT in patients with mCSPC.3
At 24 months, the rate of rPFS was 70.3% in the darolutamide arm vs 52.1% in the placebo arm, translating to a 46% reduction in the risk of radiographic progression or death (HR, 0.54; 95% CI, 0.41-0.71; P < .0001). The median rPFS was not reached in the darolutamide arm, compared with 25.0 months (95% CI, 19 to NR) in the placebo arm.
According to the authors, all subgroups derived benefit from treatment with darolutamide plus ADT. The HR for high-volume disease was 0.60 (95% CI, 0.44-0.80), and the HR for low-volume disease was 0.30 (0.15-0.60).
In a final analysis of the data, there was no statistically significant improvement in overall survival (OS) with the addition of darolutamide (HR, 0.78; 95% CI, 0.58 to 1.05). At 24 months, the OS rate was 79.8% in the darolutamide arm and 75.5% in the placebo arm.
In total, the double-blind, global ARANOTE trial included 669 patients who were randomly assigned 2:1 to receive 600 mg darolutamide twice daily plus ADT (n = 446) or to matching placebo plus ADT (n = 223).4 The median age of participants was 70 years. Among all participants, 31% were Asian and 9.7% were Black.
The primary end point for the trial was rPFS. Secondary end points included OS, time to castration-resistant prostate cancer, time to prostate-specific antigen (PSA) progression, time to pain progression, time to subsequent systemic anticancer therapy, and safety.
Data from the trial, which were published in the Journal of Clinical Oncology,2 also showed improvements in the trial's key secondary end points with the addition of darolutamide.
Specifically, darolutamide was associated with a trend toward clinical benefit in the secondary end points of time to metastatic castration-resistant prostate cancer (HR, 0.40; 95% CI, 0.32 to 0.51) and time to PSA progression (HR, 0.31; 95% CI, 0.23 to 0.41). Additionally, 62.6% of patients in the darolutamide arm achieved a PSA less than 0.2 ng/mL at any point during the treatment period, compared with 18.5% of patients in the placebo arm.
Time to pain progression (HR, 0.72; 95% CI, 0.54 to 0.96), and time to subsequent systemic anticancer therapy (HR, 0.40; 95% CI, 0.29 to 0.56) were also delayed in the darolutamide arm.
Regarding safety, the combination was well-tolerated across both study arms. The incidence of treatment-emergent adverse events (TEAEs) was similar between the 2 groups, with TEAEs leading to permanent discontinuation of study drug occurring in 6.1% of patients in the darolutamide arm and 9.0% of patients in the placebo/ADT arm. No new safety signals were reported.
REFERENCES
1. FDA approves darolutamide for metastatic castration-sensitive prostate cancer. News release. US Food & Drug Administration. Published online and accessed June 3, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-darolutamide-metastatic-castration-sensitive-prostate-cancer
2. U.S. FDA approves NUBEQA (darolutamide) to treat patients with metastatic castration-sensitive prostate cancer. News release. Bayer. Published online and accessed June 3, 2025. https://www.bayer.com/en/us/news-stories/metastatic-castration-sensitive-prostate-cancer
3. Saad F, Vjaters E, Shore N, et al. Darolutamide in combination with androgen-deprivation therapy in patients with metastatic hormone-sensitive prostate cancer from the phase III ARANOTE trial. J Clin Oncol. 2024 Sep 16:JCO2401798. doi:10.1200/JCO-24-01798
4. Darolutamide in addition to ADT versus ADT in metastatic hormone-sensitive prostate cancer (ARANOTE). ClinicalTrials.gov. Last updated November 21, 2024. Accessed June 3, 2025. https://clinicaltrials.gov/study/NCT04736199
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